Monitoring immune responsiveness to cancer vaccination

Abstract

The invention is direct to a method for determining a cancer patient's immune responsiveness to anti-cancer vaccination. In one aspect, for each of a plurality of vaccinations, pairs of clonotype profiles are obtained, one immediately prior to vaccination and one during the period of peak immune response, usually within two to twenty days after the vaccination. Responsiveness is correlated to successive increases in identical clonotypes within each pair of clonotype profiles in at least two successive vaccinations.

Description

[0001]This application claims priority under U.S. provisional patent application Ser. No. 61 / 606,653 filed 5 Mar. 2012, which application is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Cancer immunotherapy has been an attractive and difficult field. Evidence of immunosurveillance and immuno editing of cancerous cells suggests that efficient and effective cancer therapies may be attainable by informed manipulation of the immune system, e.g. Schreiber et al, Science, 331: 1565-1570 (2011); Brody et al, J. Clin. Oncol., 29: 1864-1875 (2011); Klebanoff et al, Immunological Reviews, 239: 27-44 (2011). Results of such approaches to date have been inconclusive, but tantalizing, which is due in part to the complexity and still limited understanding of many features of cancer and the immune system, including such features as exhaustion of tumor-reactive T cell populations, immunosuppression by regulatory T cells in tumors, mutability of tumor antigens, a...

AI Technical Summary

Benefits of technology

[0006]In one aspect, the invention includes a method of measuring immune responsiveness of a patient to a cancer vaccine, the method comprising the steps of (a) generating a pair of clonotype profiles at each of a plurality of successive vaccinations of a patient with a cancer vaccine, wherein a first clonotype profile of each pair is from a sample from the patient prior to vaccination and a second clonotype profile of each pair is from a sample from the patient after vaccination at a time within a peak immune response to vaccination, each clonotype profile comprising at least 1000 sequence reads of at least 30 nucleotides; and (b) correlating immune responsiveness of the patient to the cancer vaccine with an increase of identical clonotypes within each pair of clonotype profiles of at least two successive vaccinations. In this and other embodiments, the size and type of clonotype profiles used with the method may vary widely. In some embodiments, clonotype profiles comprise at least 103 clonotypes; in other embodiments, clonotype profiles comprise at least 104 clonotypes; in still other embodiments, clonotype profiles comprise at least 105 clonotypes. In some embodiments, rearranged nucleic acids of clonotypes may be 25-200 nucleotide segments of a VDJ rearrangement of IgH, a DJ rearrangement of IgH, a VJ rearrangement of IgK, a VJ rearrangement of IgL, a VDJ rearrangement of TCR β, a DJ rearrangement of TCR β, a VJ rearrangement of TCR α, a VJ rearrangement of TCR γ, a VDJ rearrangement of TCR δ, a VD rearrangement of TCR δ, a Kde-V rearrangement, or the like. In another embodiment, rearranged nucleic acids of clonotypes may be 25-200 nucleotide segments of a VDJ rearrangement of TCR β, a DJ rearrangement of TCR β, a VJ rearrangement of TCR α, a VJ rearrangement of TCR γ, a VDJ rearrangement of TCR δ, or a VD rearrangement of TCR δ. In still other embodiments, rearranged nucleic acids of clonotypes may be 25-200 nucleotide segments of a VDJ rearrangement of TCR β.

Problems solved by technology

Cancer immunotherapy has been an attractive and difficult field.

Results of such approaches to date have been inconclusive, but tantalizing, which is due in part to the complexity and still limited understanding of many features of cancer and the immune system, including such features as exhaustion of tumor-reactive T cell populations, immunosuppression by regulatory T cells in tumors, mutability of tumor antigens, and the like, e.g. Turcotte et al, Adv. Surg. 45: 341-360 (2011).

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